[Skip to Content]
[Skip to Content Landing]
Views 4,055
Citations 0
Original Investigation
January 30, 2017

Retinal Architecture and Melanopsin-Mediated Pupillary Response CharacteristicsA Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis

Author Affiliations
  • 1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas
  • 2Department of Neurology, Michigan State University, East Lansing
  • 3Center for Engineering Innovation, University of Texas at Dallas
  • 4Student, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas
  • 5Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland
  • 6Department of Neurology, Population Health, New York University School of Medicine, New York
  • 7Department of Bioengineering, University of Texas at Dallas
  • 8Department of Ophthalmology, University of Iowa, Iowa City
  • 9Iowa City Veterans Affairs Center for Prevention and Treatment of Visual Loss, Iowa City
  • 10Department of Ophthalmology, New York University School of Medicine, New York
  • 11Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas
JAMA Neurol. Published online January 30, 2017. doi:10.1001/jamaneurol.2016.5131
Key Points

Question  What is the association between the melanopsin-mediated sustained pupillary constriction response with retinal architecture in multiple sclerosis?

Findings  In a case-control study of 24 patients with multiple sclerosis, ganglion cell layer and inner plexiform layer thinning determined by optical coherence tomography corresponded to a significant attenuation of the melanopsin-mediated sustained pupillary constriction response.

Meaning  Multiple sclerosis damage to retinal architecture indicates attenuation of the melanopsin-mediated sustained pupillary constriction response, with potential relevance for retinohypothalamic modulation of homeostatic mechanisms in health and in illness.

Abstract

Importance  A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments.

Objective  To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response.

Design, Setting, and Participants  The case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL).

Main Outcomes and Measures  Association of pupillary response characteristics with alterations in retinal architecture.

Results  Of 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography–derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations).

Conclusions and Relevance  In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.

×